Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells. PNH is related to a somatic mutation in the phosphatidilinositol Glycan class A (PIG-A), X-linked gene, responsible for a deficiency in glycosyl phosphatidilinositol-anchored proteins (GPI-AP). The lack of one of the GPI-AP complement regulatory proteins (CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure or episodes of venous thrombosis. The diagnosis is based on flow cytometry, which allowed direct quantification of the GPI-AP-deficient cells. From earlier descriptions, the clinical polymorphism of PNH has been recognized by two presentations; one form, predominantly haemolytic without overt marrow failure, referred to Classic PNH, and the other one, with marrow failure, was often described as the aplastic anemia PNH syndrome (AA-PNH). Thromboses remain a major life threatening complication affecting outcomes in each of the disease subcategories. Thrombotic events are characterized by involvement of unusual sites (hepatic, mesenteric, cerebral, dermal veins). In classic PNH, recent studies have focused on inhibiting the complement cascade with encouraging clinical results using Eculizumab, a C5-inhibitor humanized monoclonal antibody. Concerning the AA-PNH syndrome, bone marrow transplantation (BMT) is the reference treatment in young patients with a sibling donor. Immunosuppressive therapy remains an important treatment modality in this subcategory for patients without a donor or ineligible for BMT. Recurrent thrombotic events remains even now associated with bad prognosis, whatever the form of the disease.
- Aplastic anemia
- Glycosyl phosphatidi-linositol-anchored proteins (GPI-AP)
- Paroxysmal nocturnal hemoglobinuria